O6-methylguanine-DNA Methyltransferase (MGMT) can specifically repair the DNA demage Induced by chioroethylnitrosoureas (CENU) such at 1-(4-amino-2-methyt-pyrlmidinyl) methyl-3-(2-chloroethyl-)-3-nitrosourea (ACNU), c...O6-methylguanine-DNA Methyltransferase (MGMT) can specifically repair the DNA demage Induced by chioroethylnitrosoureas (CENU) such at 1-(4-amino-2-methyt-pyrlmidinyl) methyl-3-(2-chloroethyl-)-3-nitrosourea (ACNU), constituting the molecular basis of tumor cell resistance to CENU. The present study demonstrated that sensitization of resistant tumor cells to ACNU could be achieved by streptozotocin (STZ) treatment which could deplete MGMT activity in vitro and in vivo. It suggested that depletion of the molecular basis of tumor cell resistance to chemotherapeutic agents might be a practicable way to improve the effectiveness of tumor chemotherapy.展开更多
Drug resistance is still one of the major problems in cancer therapy. However, during the past several years, many efforts have been focused on reversing or depleting the molecular basis of drug resistance along with ...Drug resistance is still one of the major problems in cancer therapy. However, during the past several years, many efforts have been focused on reversing or depleting the molecular basis of drug resistance along with the elucidating of the mechanisms involved.Nitrosourea compounds such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) are an important class of useful antitumor drugs. They exert their antitumor activity by alkylating the O^6 position of guanine and leading to a DNA interstrand cross-link. Introcellular O^6-methylguanine-DNA methyltransferase (O^6-MT) can repair the mentioned DNA lesions and thus plays an important role in determining the sensitivity of展开更多
Two kinds of human tumor cell strains having different activity of O^6-methylguanine-DNA methyltransferase (O^6-MT) were transplanted into nude mice. Then the mice were inject-ed intraperitoneally with bifunctional al...Two kinds of human tumor cell strains having different activity of O^6-methylguanine-DNA methyltransferase (O^6-MT) were transplanted into nude mice. Then the mice were inject-ed intraperitoneally with bifunctional alkylating agent 1--(4--amino--2-methyl--5--pyrimidinyl)methy1-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The tumors with low O^6-MTactivity were quickly suppressed or cured. The result suggests that some tumors, if previ-sionally determined with low O^6-MT activity, might be efficiently cured by treatment withACNU. This probably opens a new way for human cancer chemotherapy.展开更多
文摘O6-methylguanine-DNA Methyltransferase (MGMT) can specifically repair the DNA demage Induced by chioroethylnitrosoureas (CENU) such at 1-(4-amino-2-methyt-pyrlmidinyl) methyl-3-(2-chloroethyl-)-3-nitrosourea (ACNU), constituting the molecular basis of tumor cell resistance to CENU. The present study demonstrated that sensitization of resistant tumor cells to ACNU could be achieved by streptozotocin (STZ) treatment which could deplete MGMT activity in vitro and in vivo. It suggested that depletion of the molecular basis of tumor cell resistance to chemotherapeutic agents might be a practicable way to improve the effectiveness of tumor chemotherapy.
基金Project supported by the National Natural Science Foundation of China.
文摘Drug resistance is still one of the major problems in cancer therapy. However, during the past several years, many efforts have been focused on reversing or depleting the molecular basis of drug resistance along with the elucidating of the mechanisms involved.Nitrosourea compounds such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) are an important class of useful antitumor drugs. They exert their antitumor activity by alkylating the O^6 position of guanine and leading to a DNA interstrand cross-link. Introcellular O^6-methylguanine-DNA methyltransferase (O^6-MT) can repair the mentioned DNA lesions and thus plays an important role in determining the sensitivity of
基金Project supported by the National Natural Science Foundation of China.
文摘Two kinds of human tumor cell strains having different activity of O^6-methylguanine-DNA methyltransferase (O^6-MT) were transplanted into nude mice. Then the mice were inject-ed intraperitoneally with bifunctional alkylating agent 1--(4--amino--2-methyl--5--pyrimidinyl)methy1-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The tumors with low O^6-MTactivity were quickly suppressed or cured. The result suggests that some tumors, if previ-sionally determined with low O^6-MT activity, might be efficiently cured by treatment withACNU. This probably opens a new way for human cancer chemotherapy.
